Novel high-intensive cholesterol-lowering therapies do not ameliorate knee OA development in humanized dyslipidemic mice

Objective: High systemic cholesterol levels have been associated with osteoarthritis (OA) development. Therefore, cholesterol lowering by statins has been suggested as a potential treatment for OA. We investigated whether therapeutic high-intensive cholesterol-lowering attenuated OA development in dyslipidemic APOE*3Leiden.CETP mice. Methods:...

High-fat feeding primes the mouse knee joint to develop osteoarthritis and pathologic infrapatellar fat pad changes after surgically induced injury

Objective. Obesity is one of the greatest risk factors for osteoarthritis (OA) and evidence is accumulating that inflammatory mediators and innate immunity play an important role. The infrapatellar fat pad (IPFP) could be a potential local source of inflammatory mediators in the knee. Here, we combine surgical joint damage with high-fat feeding...

Osteoarthritis: at the crossroads of metabolism and inflammation [Artrose: op het snijvlak van metabolisme en ontsteking]

This thesis aimed to investigate how metabolic overload contributes to the pathophysiology of knee OA. We explored the role of these independent yet intertwined processes using state-of-the-art lipidomic and cellular approaches in mouse models of diet-induced OA. Chapter 2 presents an overview of twelve preclinical studies in which mice received...

Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet

Objective. C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP ...

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought

Objective. Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was...

Metabolic dysregulation accelerates injury-induced joint degeneration, driven by local inflammation; an in vivo rat study

Evidence is growing for the existence of an obesity-related phenotype of osteoarthritis in which low-grade inflammation and a disturbed metabolic profile play a role. The contribution of an obesity-induced metabolic dysbalance to the progression of the features of osteoarthritis upon mechanically induced cartilage damage was studied in a rat in...